Leukemia — Types, Causes, Symptoms & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Leukemia is a cancer of blood-forming tissues including bone marrow and the lymphatic system. Classified as acute (ALL, AML) or chronic (CLL, CML) and lymphoid or myeloid, there are over 470,000 new cases globally per year. Children and adults over 65 are most commonly affected.Leukaemia is a malignancy of blood-forming tissues — bone marrow and the lymphatic system — characterised by uncontrolled proliferation of abnormal blood cells that crowd out normal blood cell production. It is classified by the rate of progression (acute versus chronic) and the lineage of origin (lymphoid versus myeloid), yielding four main types: acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL), and chronic myeloid leukaemia (CML). There are approximately 470,000 new leukaemia cases and 310,000 deaths globally per year. Acute leukaemias present suddenly and are rapidly fatal within weeks to months without treatment; chronic leukaemias typically progress slowly over years and may be managed rather than cured in many patients. The 5-year overall survival for all leukaemia types combined is approximately 65% in high-income countries — significantly improved from 33% in 1975 due to targeted therapies and stem cell transplantation. ALL in children has 5-year survival above 85–90%, representing one of the greatest oncological success stories.

Risk factors include ionizing radiation exposure, benzene and chemical toxin exposure, prior chemotherapy or radiotherapy, Down syndrome and other genetic disorders, family history, and smoking. The Philadelphia chromosome (BCR-ABL1 fusion) is characteristic of CML. Most cases have no identifiable cause.Ionising radiation — including medical X-ray exposure (particularly in utero), nuclear fallout (Hiroshima, Chernobyl survivors — 10-fold increased leukaemia risk), and therapeutic radiotherapy — is a well-established leukaemia risk factor. Benzene exposure — from occupational settings (petroleum refining, rubber manufacturing, shoe production) and cigarette smoke — is the best-characterised chemical carcinogen causing AML. Prior cytotoxic chemotherapy (alkylating agents — cyclophosphamide, busulfan, melphalan; topoisomerase II inhibitors — doxorubicin, etoposide) cause therapy-related AML and MDS, typically occurring 2–10 years after treatment and carrying a worse prognosis than de novo AML. Genetic syndromes with elevated leukaemia risk: Down syndrome (trisomy 21) — 10–20 times increased ALL risk; Fanconi anaemia (FANC gene mutations — chromosomal instability) — high AML risk; ataxia telangiectasia (ATM mutation — DNA repair defect) — ALL and lymphoma risk; Bloom syndrome; and Li-Fraumeni syndrome (TP53 germline mutation). The Philadelphia chromosome t(9;22)(q34;q11) — BCR-ABL1 fusion oncogene — is present in virtually all CML and 25% of adult ALL cases.

Fatigue, pallor, frequent infections, easy bruising, petechiae, bone pain, lymphadenopathy, splenomegaly, night sweats, unexplained weight loss, and fever are characteristic symptoms. Acute leukemia presents suddenly and deteriorates rapidly; chronic leukemia may be asymptomatic for years.Anaemia symptoms (fatigue, pallor, dyspnoea on exertion, palpitations) from replacement of normal red cell precursors by leukaemic blasts. Thrombocytopenic bleeding — easy bruising (ecchymoses), petechiae (pinpoint haemorrhages in skin and mucous membranes from platelet counts below 50,000/µL), epistaxis, gingival bleeding, and in severe cases intracranial haemorrhage (the most feared complication of profound thrombocytopenia). Recurrent bacterial and fungal infections from neutropenia (granulocyte count below 500/µL predicts highest infection risk) — presenting as recurrent fever, pneumonia, and skin infections. Bone pain and joint pain — from leukaemic infiltration of bone marrow and periosteum — is particularly prominent in ALL in children and may be misdiagnosed as arthritis or bone pain from other causes. Lymphadenopathy, splenomegaly (sometimes massive in CML and CLL), and hepatomegaly from organ infiltration by leukaemic cells. B symptoms (weight loss above 10% body weight in 6 months, drenching night sweats, unexplained fevers above 38°C) indicate systemic disease activity. CLL may present as an incidental finding of lymphocytosis on routine blood count with no symptoms. CML presents with insidious fatigue, weight loss, abdominal discomfort from splenomegaly, and is often diagnosed incidentally. CNS involvement in ALL causes headaches, vomiting, cranial nerve palsies, and meningism — CNS prophylaxis (intrathecal methotrexate and/or cranial irradiation) is standard in ALL treatment.

Complete blood count (CBC) with differential, peripheral blood smear, bone marrow biopsy and aspiration, flow cytometry for immunophenotyping, cytogenetics, FISH, and molecular testing (PCR for BCR-ABL1) are essential. Lumbar puncture assesses CNS involvement in ALL.Complete blood count (CBC) with differential: leukaemia typically shows leukocytosis (elevated WBC — sometimes dramatically elevated to 100,000–300,000/µL in AML and CML), anaemia, and thrombocytopenia. Leukaemic blasts on peripheral blood smear are the initial diagnostic finding — Auer rods (azurophilic cytoplasmic inclusions) are pathognomonic of AML. Bone marrow aspiration and trephine biopsy: defines blast percentage (above 20% blasts in AML; above 25% in ALL), marrow cellularity, and morphology. Flow cytometry (immunophenotyping) classifies leukaemia by surface markers: CD markers distinguish B-cell ALL (CD19, CD10, CD22), T-cell ALL (CD3, CD7), AML (CD33, CD34, HLA-DR, CD117), CLL (CD5/CD23 co-expression distinguishes from other B-cell malignancies), and CML myeloid markers. Cytogenetics (karyotype): identifies chromosomal abnormalities that guide prognosis and treatment — t(15;17) APL (acute promyelocytic leukaemia — treated with ATRA), t(8;21) favourable AML, inv(16) favourable AML, complex karyotype poor-prognosis AML. FISH (fluorescence in situ hybridisation): detects BCR-ABL1 (CML, Philadelphia-positive ALL), MLL rearrangements, and other specific translocations with higher sensitivity than conventional karyotype. Molecular PCR: quantitative BCR-ABL1 monitoring guides TKI dose adjustments and treatment-free remission decisions in CML. Lumbar puncture: mandatory in ALL to assess CNS involvement — intrathecal chemotherapy administered simultaneously for prophylaxis. MRI brain and spine if CNS symptoms present.

ALL: induction, consolidation, and maintenance chemotherapy with CNS prophylaxis. AML: intensive chemotherapy with daunorubicin and cytarabine. CML: tyrosine kinase inhibitors (imatinib, nilotinib, dasatinib) are first-line. CLL: ibrutinib, venetoclax. Allogeneic stem cell transplant for high-risk or relapsed disease.ALL in adults and children: intensive multiagent induction chemotherapy (vincristine, daunorubicin, L-asparaginase, corticosteroids — BFM, UKALL, or COG protocol depending on age); consolidation and maintenance phases (24–36 months total); CNS prophylaxis (intrathecal methotrexate, cranial irradiation reserved for high-risk CNS disease). Philadelphia-positive ALL (25% of adult ALL): TKI (imatinib, dasatinib, or ponatinib) added to chemotherapy — dramatically improves outcomes. AML (non-APL): intensive induction 7+3 (continuous cytarabine infusion 100–200 mg/m² for 7 days plus daunorubicin 3 days — or idarubicin), achieving CR in 60–80%; consolidation with high-dose cytarabine (HiDAC) or allogeneic stem cell transplant (alloSCT) for high-risk disease. APL: all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) — the AIDA and APL0406 protocols — cures 85–90% of APL without conventional chemotherapy. Targeted therapy: FLT3 inhibitors (midostaurin, quizartinib — for FLT3-mutated AML), IDH1/2 inhibitors (ivosidenib, enasidenib), venetoclax (BCL-2 inhibitor) combined with azacitidine for older unfit AML patients — achieves CR rates of 65–70% in this population. CML: imatinib (Gleevec) — first TKI, transformed CML from a fatal disease to a chronic manageable condition; second-generation TKIs (nilotinib, dasatinib, bosutinib) achieve faster and deeper molecular responses; ponatinib for T315I mutation. Treatment-free remission (TFR): after sustained deep molecular response (MR4.5 — BCR-ABL1 below 0.0032%) for 2+ years, TKI discontinuation achieves sustained TFR in 40–50%. CLL: asymptomatic CLL may be observed for years without treatment ('watch and wait'); treatment initiated for symptomatic disease — ibrutinib (BTK inhibitor) or acalabrutinib monotherapy for most patients; venetoclax (BCL-2 inhibitor) + obinutuzumab for time-limited treatment option. Allogeneic stem cell transplant (alloSCT): curative intent for high-risk ALL, AML in CR2, CML not responding to TKIs — graft-versus-leukaemia (GVL) effect from donor immune cells attacks residual leukaemia. CAR-T cell therapy: CD19-directed CAR-T (tisagenlecleucel — Kymriah; axicabtagene ciloleucel — Yescarta) achieves CR rates of 70–90% in heavily pre-treated relapsed/refractory B-ALL and diffuse large B-cell lymphoma — a transformational therapeutic advance.

Neutropenic infection is the leading cause of treatment-related death. Thrombocytopenic bleeding, severe anemia, tumor lysis syndrome, CNS disease, and secondary malignancies are serious complications. Stem cell transplant carries risks of graft-versus-host disease and opportunistic infections.Neutropenic sepsis (infection in the setting of neutrophil count below 500/µL) is a haematological emergency requiring immediate blood cultures and broad-spectrum IV antibiotics within 1 hour of fever onset (Tazocin or meropenem ± gentamicin ± antifungal); the MASCC risk score guides safe outpatient management of low-risk febrile neutropenia. Tumour lysis syndrome (TLS) — massive release of intracellular contents (uric acid, potassium, phosphate) when large tumour burden is rapidly killed by initial chemotherapy — causes acute kidney injury, hypocalcaemia (from hyperphosphataemia — tetany, seizures), fatal cardiac arrhythmia from hyperkalaemia, and uric acid nephropathy; prevented and treated with aggressive IV hydration, allopurinol or rasburicase. Haemorrhage from severe thrombocytopenia (platelets below 10,000–20,000/µL) — intracranial haemorrhage, gastrointestinal bleeding, and pulmonary haemorrhage are potentially fatal; treated with platelet transfusions. Graft-versus-host disease (GvHD) after alloSCT: acute GvHD (within 100 days — skin rash, diarrhoea, liver dysfunction, treated with high-dose methylprednisolone); chronic GvHD (after 100 days — multi-organ fibrosis and inflammation, treated with ruxolitinib, ibrutinib, or extracorporeal photopheresis). Secondary malignancies from chemotherapy and radiotherapy — therapy-related AML, MDS, secondary solid tumours — develop in 5–15% of long-term leukaemia survivors. Anthracycline-induced cardiomyopathy requires cardiac monitoring with echocardiography before, during, and after treatment.

Avoid benzene exposure and excessive ionizing radiation. No targeted prevention exists for most leukemia subtypes. Genetic counseling is recommended for familial leukemia syndromes such as Fanconi anemia. Surveillance for high-risk individuals, including those with prior cytotoxic therapy, is advised.There is no proven primary prevention for most leukaemia subtypes. Minimise occupational benzene exposure through industrial hygiene measures, protective equipment, and regulatory exposure limits. Avoid unnecessary ionising radiation — follow ALARA (as low as reasonably achievable) principles for medical imaging, especially in children and young adults. Smoking cessation reduces leukaemia risk (AML risk is 40% higher in smokers). Healthy weight maintenance (obesity increases AML risk through adipose-derived inflammatory mediators). For individuals at high genetic risk (Down syndrome, Fanconi anaemia, BRCA carriers treated with chemotherapy): regular surveillance with CBC at 6–12 monthly intervals from an early age enables early detection before advanced disease. Genetic counselling for first-degree relatives of patients with familial leukaemia syndromes (inherited TP53, RUNX1, CEBPA mutations).

See your GP urgently — within 24-48 hours — for: persistent unexplained fatigue and pallor not responding to rest, recurrent infections not resolving normally, unexplained bruising or bleeding (petechiae, frequent nosebleeds, heavy periods), painless persistent lymph node enlargement lasting more than 4 weeks, or bone pain without injury. Acute leukaemia can be rapidly fatal within weeks without treatment — symptoms can progress very quickly and should never be dismissed as a viral illness. Go to A&E immediately if you have a confirmed leukaemia diagnosis for: fever above 38.5°C during chemotherapy (neutropenic sepsis — a haematological emergency requiring immediate IV broad-spectrum antibiotics), severe bleeding that cannot be controlled, sudden severe bone pain, or neurological symptoms (severe headache, confusion, visual changes — possible CNS leukaemia). An incidental finding of abnormal white cell count on any routine blood test warrants same-day GP phone consultation and urgent review within 48 hours.